VCV001180547.4 - ClinVar

GRCh37/hg19 5p15.33(chr5:13200-4012072)x1

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(1)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

GRCh37/hg19 5p15.33(chr5:13200-4012072)x1

Variation ID: 1180547 Accession: VCV001180547.4

Type and length

copy number loss, 3,998,873 bp

Location

Cytogenetic: 5p15.33 5: 13200-4012072 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Jul 24, 2021	Jul 24, 2021	Jan 9, 2019

HGVS

Protein change

Other names

Canonical SPDI

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
TERT		Little evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	2984	3427
SLC6A18		Dosage sensitivity unlikely	No evidence available	GRCh38 GRCh37	86	243
AHRR		-	-	GRCh38 GRCh37	1	241
BRD9		-	-	GRCh38 GRCh37	38	196
CCDC127	-	-	-	GRCh38 GRCh37	27	178
CEP72		-	-	GRCh38 GRCh38 GRCh37	58	241
CLPTM1L		-	-	GRCh38 GRCh38 GRCh37	60	207
EXOC3		-	-	GRCh38 GRCh37	58	210
EXOC3-AS1	-	-	-	GRCh38 GRCh37	-	150
IRX1		-	-	GRCh38 GRCh37	53	180

There are 19 more genes affected by this variant. See the full set of genes in Variation Viewer (GRCh37) and ClinGen Dosage Sensitivity Map.

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
not provided	Pathogenic (1)	criteria provided, single submitter	Jan 9, 2019	RCV001537929.4

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Jan 09, 2019)	criteria provided, single submitter (ICSL CNVClassificationCriteria Jul2020Prior) Method: clinical testing	not provided Affected status: unknown Allele origin: unknown	Illumina Laboratory Services, Illumina Accession: SCV001754857.1 First in ClinVar: Jul 24, 2021 Last updated: Jul 24, 2021	Publications: PubMed (6) PubMed: 11238681‚ 16953888‚ 25385231‚ 26235846‚ 8079991‚ 8250043 Comment: This CNV is a 4 Mb deletion of 5p15.33, on chromosome 5, (seq[GRCh37]del(5)(p15.33); chr5:g.13200_4012072del), found in a de novo state. The CNV constitutes a loss … (more) This CNV is a 4 Mb deletion of 5p15.33, on chromosome 5, (seq[GRCh37]del(5)(p15.33); chr5:g.13200_4012072del), found in a de novo state. The CNV constitutes a loss encompassing 60 genes and overlaps the well-described 5p deletion syndrome, also known as cri du chat syndrome (CdCS). CdCS has an estimated population prevalence of 1:15,000 to 1:50,000 and has been reported in more than 200 probands. Unbalanced translocations have been reported in affected individuals who inherited the derivative chromosome from a parent with a balanced translocation. Deletions ranging in size from 560 kb to 40 Mb have been observed in individuals with CdCS, and phenotypic variability has been noted in relation to the location and size of the deletion. Terminal deletions are frequently observed in affected individuals (Mainardi et al. 2001; Mainardi 2006; Nguyen et al. 2016). Common features of the syndrome include high-pitched monochromatic cry, microcephaly, broad nasal bridge, epicanthal folds, micrognathia, abnormal dermatoglyphics, and severe psychomotor and mental retardation. Additional variable features include cardiac, neurological and renal abnormalities, preauricular tags, syndactyly, hypospadias, and cryptorchidism. Based on the collective evidence, this CNV is classified as pathogenic. (less)

Comment:

This CNV is a 4 Mb deletion of 5p15.33, on chromosome 5, (seq[GRCh37]del(5)(p15.33); chr5:g.13200_4012072del), found in a de novo state. The CNV constitutes a loss encompassing 60 genes and overlaps the well-described 5p deletion syndrome, also known as cri du chat syndrome (CdCS). CdCS has an estimated population prevalence of 1:15,000 to 1:50,000 and has been reported in more than 200 probands. Unbalanced translocations have been reported in affected individuals who inherited the derivative chromosome from a parent with a balanced translocation. Deletions ranging in size from 560 kb to 40 Mb have been observed in individuals with CdCS, and phenotypic variability has been noted in relation to the location and size of the deletion. Terminal deletions are frequently observed in affected individuals (Mainardi et al. 2001; Mainardi 2006; Nguyen et al. 2016). Common features of the syndrome include high-pitched monochromatic cry, microcephaly, broad nasal bridge, epicanthal folds, micrognathia, abnormal dermatoglyphics, and severe psychomotor and mental retardation. Additional variable features include cardiac, neurological and renal abnormalities, preauricular tags, syndactyly, hypospadias, and cryptorchidism. Based on the collective evidence, this CNV is classified as pathogenic.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
5p deletions: Current knowledge and future directions.	Nguyen JM	American journal of medical genetics. Part C, Seminars in medical genetics	2015	PMID: 26235846
When Cri du chat syndrome meets Edwards syndrome.	Xie Y	Molecular medicine reports	2015	PMID: 25385231
Cri du Chat syndrome.	Cerruti Mainardi P	Orphanet journal of rare diseases	2006	PMID: 16953888
Clinical and molecular characterisation of 80 patients with 5p deletion: genotype-phenotype correlation.	Mainardi PC	Journal of medical genetics	2001	PMID: 11238681
Molecular mapping of the Edwards syndrome phenotype to two noncontiguous regions on chromosome 18.	Boghosian-Sell L	American journal of human genetics	1994	PMID: 8079991
Clinical and molecular evaluation of four patients with partial duplications of the long arm of chromosome 18.	Mewar R	American journal of human genetics	1993	PMID: 8250043

Text-mined citations for this variant ...

Record last updated Apr 09, 2023

ClinVar Genomic variation as it relates to human health

GRCh37/hg19 5p15.33(chr5:13200-4012072)x1

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...